As the development of new methods that directly assess neural activity becomes a pressing need, a variety of optical techniques is being investigated for imaging neural structure and function with high temporal and spatial resolutions. Recently, the emerging technology of spectral-domain optical coherence tomography (OCT) has allowed us to simultaneously detect action potential (AP) related phase changes at different depths from invertebrate axons on a millisecond time scale. We also utilized the technology for depth- localization of APs in axons stained with voltage-sensitive dyes, and constructed highly sensitivity polarization-sensitive systems for measuring retardance change during AP propagation. These techniques have the additional advantage of being less invasive than many other measurements, because they work in reflection geometry, which means the source and detector are on the same side of the nerve. The long term goal is to provide clinically useful noninvasive tests of nerve function. The overall objective of this project is to develop phase- and polarization-sensitive OCT techniques and contrast enhancement methods for depth-resolved imaging of neural activity in various preparations including squid giant axon, pike olfactory nerve, and salamander and mouse retinas. The objective includes development of insights about the nature and origin of the optically recorded signals. Presently, the mechanistic origins of the structural changes producing the optical signals are not known. The lack of knowledge hampers improvements in the assessment of neural activity. Furthermore, development of new techniques and contrasts is essential for scientific and clinical applications. PUBLIC HEALTH RELEVANCE: The focus of this proposal is to image transient structural changes during physiological activity (function) prior to any anatomical structural loss or permanent damage in neural tissue. By developing novel non-contact non-invasive optical imaging techniques, we intend to find the most favorable optical measures of neural activity that can be utilized for early detection of neural diseases.